Introduction: Ovarian cancer is one of the most common gynecological cancers in the United States. Common sites of distant metastasis from ovarian cancers and other cancers of Mullerian origin include the liver, pleura and lungs. However, metastasis to the brain remains exceptionally rare, ranging from 0.49 to 6.1%. Hence, the scarcity of such cases poses significant diagnostic and management challenges. Case Presentation: We present a case of an 80-year-old female who at the time of initial diagnosis presented with complaints of right leg pain, shortness of breath and cough. Imaging studies were remarkable for a pulmonary embolism, 2.5 cm mediastinal mass, pleural effusions, omental caking and an occlusive thrombus in the right greater saphenous vein. Malignancy was suspected in the setting of hypercoagulability. Biopsy of the omentum and pleural cytology revealed a high grade ovarian serous carcinoma. The patient received neoadjuvant chemotherapy followed by cytoreductive surgery and additional chemotherapy afterwards. She demonstrated good response to treatment with follow up PET without evidence of disease. Over the next four years, the patient was intermittently placed on chemotherapy when found to have elevated CA125 levels and PET scan showing small volume disease mostly in the pelvis. Six-years later, the patient presented to the oncology clinic with complaints of dizziness and imbalance for the past month. MRI brain showed a new left cerebellar mass with vasogenic edema and obstructive hydrocephalus. However, restaging CT chest, abdomen and pelvis showed minimal to no disease, with the only possible foci being a 1.2 cm paraaortic lymph node. The patient underwent left suboccipital craniotomy and cerebellar tumor resection with pathology showing metastatic carcinoma consistent with spread from a Mullerian primary. Conclusion: This case emphasizes the diagnostic complexity and evolving clinical course of Müllerian tumors. In a patient with a history of Mullerian tumor and new onset neurological symptoms, differential diagnosis should include metastasis to the brain, even with minimal to no active pelvic and systemic disease burden.

Chronic illnesses such as cardiovascular disease (CVD) are currently among the biggest risks to human health. The accumulation of homocysteine (Hcy) can result in platelet disorders, vascular damage, smooth muscle swelling, and ultimately occlusive thrombus development, all of which raise the risk of CVD. Hence, the sensitive and selective detection of Hcy, a critical biomarker for cardiovascular disorders, is vital for early diagnosis and clinical monitoring. In this study, we created an electrochemical sensor for the detection of Hcy using an electrode modified with a nanohybrid comprising boron–nitrogen (B–N) codoped MXene (BNM) and multiwalled carbon nanotubes (MWCNTs). The codoping of B and N increases the dispersion of MXenes, greatly expanding the effective surface area and giving a large number of electroactive sites for MWCNTs, while MWCNTs enhance electrocatalysis and inhibit restacking. Thus, both materials in conjunction can result in superior electrochemical properties. Under optimized conditions, the developed sensor exhibited excellent efficiency for Hcy detection, with a wide linear range of 2.5–400 μM, which covers the normal as well as clinical range. It possesses a detection limit of 0.39 ± 0.02 μM and a response time of 2.6 ± 0.14 s. The sensor demonstrated high selectivity in the presence of common interfering species and excellent reproducibility and stability, making it suitable for practical applications. Furthermore, the smartphone application “HomoCysCheck” was developed to rapidly calculate Hcy concentrations and distinguish between safe and unsafe levels in real samples. This work provides a simple and rapid detection platform for Hcy, offering significant potential for use in point-of-care applications.

Establishing updated diagnostic reference levels for interventional radiology: a national Italian survey incorporating procedure complexity indices - Part II: interventional neuroradiology.

Left ventricular thrombus and thromboembolic occlusion seen with point of care ultrasound

A woman in her 50s with Factor V Leiden and recent surgery with history of multiple right-sided deep venous thromboses not on anticoagulation due to a prior bleeding complication presented with acute left groin pain and discolouration. Physical exam was concerning for a condition in which a large blood clot blocks the major deep veins of the legs causing painful swelling and a pale appearance. CT imaging revealed a massive occlusive thrombus. Point of care ultrasound was significant for a completely collapsed inferior vena cava. The patient's presentation progressed, and she subsequently underwent clot removal and was started on Heparin for anticoagulation. She was subtherapeutic on heparin and was started on argatroban. On discharge, she was transitioned to fondaparinux.

Occlusive thrombi within blood vessels are a primary cause of life-threatening cardiovascular diseases, which continue to pose significant global health challenges. Here, we report a polymer nanoplatform that integrates near-infrared II (NIR-II) light-triggered photothermal thrombolysis with intrinsic antithrombotic functionality. A novel semiconducting polymer, featuring intense NIR-II absorption and exceptionally high photothermal conversion, is rationally engineered to enable rapid and localized light-to-heat thrombolysis. A thermosensitive hydrogen sulfide (H2S) donor is also incorporated, generating multifunctional "nanosweepers" that combine synergistic photothermal and gas-mediated thrombolytic activity. The formulation is further functionalized with bis-serotonin groups, which confer myeloperoxidase- and hydrogen peroxide-responsive thrombus-targeting capability, ensuring selective accumulation and site-specific therapy. This agent possesses robust NIR-II absorption, high photothermal conversion efficiency (77.2%), and pronounced thrombus-specific enrichment. Importantly, the combination of localized photothermal heating and on-demand H2S release enable rapid, near-complete thrombolysis in both carotid and lower-limb arterial thrombosis models, achieving almost full restoration of blood flow. This work establishes a versatile and highly efficient strategy that integrates precise NIR-II photothermal conversion with H2S-mediated redox regulation, providing a promising platform for site-specific multimodal synergistic treatment of life-threatening thrombotic disorders. The findings offer new insights into the design of multifunctional, precision therapeutics for vascular disease management.

The Na/K-ATPase α1 subunit fine-tunes platelet P2Y12 function and mediates sex dimorphism-associated thrombosis.

Background: Platelet hyperreactivity contributes to occlusive thrombus formation in vessels, precipitating acute cardiovascular events such as myocardial infarction and stroke. Traditional Chinese Medicine (TCM) has been used for centuries, and numerous TCM herbs have been reported to exert anti-inflammatory and anticoagulant effects. Objectives: We sought to identify key compounds within the TCM-derived herbal extracts that regulate platelet activity. Methods: Crude and fractioned herbal extracts were screened for their ability to inhibit platelet activation in response to multiple agonists. Platelet aggregation and flow cytometry were used to assess the potency and selectivity of the compounds within the extracts. Results: Three extracts, di gu pi (DGP), san qi (SQ), and zi cao (ZC), demonstrated inhibitory activity and were subsequently fractionated. Fractions derived from DGP, the root bark of Lycium chinense, inhibited platelet aggregation and suppressed integrin activation and granule secretion downstream of collagen receptor signaling. Further analysis identified the oxidized lipids 9(S)-hydroxy-9Z,11E-octadecadienoic acid (9-HODE), 13(S)-HODE, and 13(S)-hydroxy-9Z,11E,15Z-octadecatrienoic acid (13-HOTrE) as constituents of the bioactive fractions. Both 13-HODE and 13-HOTrE selectively inhibited collagen-mediated platelet aggregation without affecting thrombin-induced activation. Conclusions: Collectively, these findings identify oxylipins in TCM as promising candidates for the development of antiplatelet therapies targeting platelet activity and thrombosis. These oxylipins may represent novel approaches for thrombosis and have high therapeutic potential for development as next-generation antiplatelet drugs.

SHIP1 agonist rosiptor inhibits platelet activation and thrombosis by modulating cAMP/cGMP and PI3K/PKC pathway.

Platelets are a crucial component in the maintenance of normal haemostasis. In response to vascular damage, activated platelets adhere to the damaged endothelium leading to both aggregation and coagulation. Under healthy conditions, these processes prevent excessive vascular haemorrhage and promote vascular repair and regeneration. However, in cardiovascular diseases, hyperactive platelet activation leads to acute coronary syndrome characterised by occlusive thrombus formation, myocardial infarction and stroke. Targeted platelet therapy has been used extensively in the inhibition of inappropriate platelet activation for the treatment of cardiovascular diseases including cyclooxygenase inhibitors, purinergic antagonists, thrombin inhibitors, PAR receptor antagonists, and phosphodiesterase inhibitors. In this review, we discuss the current clinical portfolio of antiplatelet therapies whilst also discussing promising new antiplatelet targets for the treatment of cardiovascular disorders.

BackgroundLactobacillus paracasei (LP) may affect the efficacy of clopidogrel (CLP).Methods Forty Sprague-Dawley (SD) rats were randomly divided into control group, LP group, CLP group, LP (pretreatment) + CLP group, and CLP + LP(posttreatment) group (n=6-8). The administration doses of CLP and LP in rats were 6.75 mg/kg/d and 109 CFU/d, respectively, for 14 consecutive days. Tail vein blood was collected to detect blood drug concentration, platelet function. Then, a thrombosis model was constructed using 20% FeCl₃, the complete vascular occlusion time, thrombus weight, and thrombus inhibition rate, inflammatory factors, gut microbiota, short-chain fatty acids (SCFAs), trimethylamine N-oxide (TMAO) and mucosal barrier were evaluated.Results Compared with the CLP group, the blood concentrations of AM and CA in the combined group were significantly decreased, while platelet aggregation (MPA) and platelet reaction index (PRI) were significantly increased. After model construction, the thrombosis formation time was significantly prolonged, the thrombus weight was significantly reduced, and the thrombus inhibition rate was significantly; the secretions of TNF-α, IL-1β, P-selectin, GPIIb/IIIa, and D-dimer were significantly decreased in the combined group. The structure of gut microbiota also changed significantly after CLP treatment, and LP combined with CLP could improve the dysbiosis caused by CLP through increasing SCFAs and decreasing TMAO. In addition, the expressions of ZO-1, Occludin, and P-gp were increased in the combined groups. It should be noted that there is a directional discrepancy between the changes in platelet function indices (MPA and PRI) and in vivo thrombosis outcomes, which may be related to the multi-factorial regulation of in vivo thrombosis.ConclusionLP may regulate the structure of gut microbiota (increasing SCFA-producing bacteria and inhibiting TMAO-producing bacteria), thereby protecting the intestinal mucosal barrier, inhibiting inflammatory responses, and cooperatively acting with CLP to inhibit platelet activation and improve coagulation function, although the specific mechanism needs further verification.

Aortic atherosclerotic plaques are more thrombogenic than carotid and femoral plaques: the role of fibrillar collagen.

This scientific article examines the key morphological changes occurring in coronary vessels and myocardial tissue during infarction, with a particular emphasis on the mechanisms of ischemic injury, the dynamics of necrotic processes, and microcirculatory responses. Myocardial infarction is one of the most studied, yet still incompletely understood, pathologies of the cardiovascular system, as the morphological presentation of the disease depends on numerous variables—the nature of atherosclerotic changes, the types of acute coronary thrombosis, the degree of collateral circulation, and the time of reperfusion. Analysis of vascular pathology reveals a complex cascade of structural abnormalities, including atheromatous intimal damage, rupture of the fibrous plaque cap, formation of a mural or occlusive thrombus, and endothelial spasm and dysfunction, which together lead to a critical reduction in coronary blood flow. During ischemia, the myocardium undergoes successive stages of morphological remodeling—from reversible cardiomyocyte damage to coagulative necrosis, the development of an acute inflammatory response, the formation of granulation tissue, and late scarring. Microcirculatory disturbances play a significant role in the development of this morphological picture: stasis, sludge phenomenon, plasma impregnation of vascular walls, capillary rupture, and diapedetic hemorrhages. These processes intensify the zone of necrosis and determine the subsequent organization of damaged tissue. The article focuses on the relationship between the morphological state of the coronary vessels and the clinical manifestations of myocardial infarction, which is of fundamental importance for diagnosis, selection of treatment tactics, and prognosis. The presented material reflects a modern view of the pathogenetic mechanisms of infarction and can serve as a basis for further research in the field of cardiopathology.

Prevalence and outcomes of inherited and acquired thrombophilia in pediatric patients with venous thromboembolism: Findings from an institutional prospective inception cohort study

Introduction Ischemic stroke in the setting of advanced malignancy poses unique challenges due to competing risks of hypercoagulability and hemorrhage. We present a case of tandem occlusion caused by a free‐floating internal carotid artery (ICA) thrombus in a patient with metastatic adenocarcinoma, highlighting individualized decision‐making in reperfusion therapy. Materials/Methods A 59‐year‐old Mandarin‐speaking woman with stage IV lung adenocarcinoma, malignant pleural effusions (with PleurX catheter), malignant ascites, recent chemotherapy (amivantamab, pemetrexed, carboplatin) and left parietal AVM presented with sudden‐onset aphasia (last known well 3 hours). On arrival, she was awake but non‐verbal, not following commands despite interpreter assistance, with subtle left gaze preference and evolving right‐sided weakness (NIHSS 16). Non‐contrast CT showed subtle left MCA ischemic changes. CTA revealed a proximal free‐floating left ICA thrombus with tandem left M2 occlusion. Given prohibitive hemorrhagic risk from malignant effusions, ascites and AVM, IV thrombolysis was withheld. She underwent urgent mechanical thrombectomy with neuro‐ICU admission. Results Reperfusion was successfully achieved, with significant improvement in language function toward her baseline. The combination of proximal free‐floating ICA thrombus and distal MCA occlusion illustrated malignancy‐associated tandem pathology within a hypercoagulable milieu. Conclusion This case underscores several key points: free‐floating ICA thrombus is a rare but important malignancy‐associated cause of tandem occlusion; cancer‐related coagulopathy can present with atypical clot morphology and recurrence risk; and reperfusion strategies must balance guideline‐based therapies against individualized bleeding risks. Mechanical thrombectomy provided safe and effective treatment where IV thrombolysis was contraindicated. Recognition of stroke in oncology patients may be delayed by language barriers, treatment effects, and overlapping symptoms. This report contributes to the limited literature on thrombectomy outcomes in cancer patients with concurrent extracranial bleeding risks and cerebrovascular anomalies. image Image 1: L ICA free‐floating thrombus (donut sign) image Image 2: L M2 LVO (tandem occlusion)

BackgroundPlaque disruption exposes thrombogenic substrates and triggers local thrombosis. When a fresh thrombus forms, endogenous antithrombotic mechanisms activate. The balance between these two pro- and antithrombotic mechanisms determines the outcome of plaque disruption. When thrombogenic stimuli outweigh the antithrombotic mechanisms, an occlusive thrombus forms, leading to acute coronary syndromes. When antithrombotic mechanisms dominate, a non-occlusive thrombus forms, contributing to the rapid progression of atherosclerosis. A layered or healed plaque can be identified using optical coherence tomography (OCT).PurposeThe study aimed to investigate the association between atherothrombotic biomarkers and layered plaque at culprit lesions.MethodsWe analyzed 119 lesions in patients with chronic coronary syndrome who underwent OCT prior to percutaneous coronary intervention. Four groups of biomarkers were studied: antithrombotic, atherogenic, prothrombotic, and inflammatory. The layer index, defined as the mean layer arc multiplied by the layer length, was assessed using OCT.ResultsPatients were divided into tertiles based on each of the four groups. Among the four groups, only the antithrombotic biomarkers were significantly associated with the layer index (low vs. moderate vs. high: 0 vs. 517 vs. 719, p for trend = 0.037). This positive correlation remained significant after adjusting for confounders. In contrast, no association was found between the layer index and atherogenic, prothrombotic, or inflammatory biomarkers.ConclusionsThe antithrombotic mechanism appears to play a key role in layered plaque formation.

Introduction to a review series on the structural underpinnings of hemostatic plugs and thrombotic occlusions.

With every increment of glomerular filtration rate (GFR) by 10%, there is an elevated risk of stroke by 7%. Stroke death is also 9 times higher in end stage renal failure (ESRF) patients as compared to the general population. Certain studies have described that intravenous thrombolysis in ESRF patients with acute ischaemic stroke has no added benefit with increased risk of bleeding while some still recommend intravenous thrombolysis (IVT) as it improves neurological outcome. We describe two cases of acute ischaemic stroke at 0 hours post haemodialysis (HD) and 3.5 hours post HD. A 62-year- old gentleman with underlying hypertension and ESRF, presented 3.5 hours after haemodialysis with National Institute of Health Stroke Scale (NIHSS) of 7. Computed Tomography Angiography (CTA) showed a right distal M1 non occlusive thrombus and IV Alteplase 40mg was given. NIHSS post IVT at 6hours showed improvement to 3 and 0 upon discharge. Current mRS is 0. Upon undergoing 3hours of haemodialysis, a 66-year-old gentleman with underlying Hepatitis C and ESRF had an acute stroke with NIHSS of 10. CTA showed left M2 occlusion and IV Alteplase 50mg was given. NIHSS 6hours post IVT is 7 and 4 upon discharge. Complications include, oozing over his left BCF and minimal sulcal subarachnoid haemorhage. Current mRS is 1. In conclusion, post dialysis patients who suffer from an acute stroke, may be given intravenous thrombolysis as to improve their clinical outcome. In this study, both patients were given a lower dose of Alteplase (0.6mg/kg) and had favourable outcomes.

Vasculitides encompass a group of inflammatory diseases that affect blood vessels, leading to vessel wall thickening, ischemia, and potential organ damage. While rare, the prevalence of vasculitis has increased in recent years. Its presentation often mimics infectious and paraneoplastic diseases, requiring the identification of risk factors and individualised diagnostic workup. Delayed or inaccurate diagnosis of vasculitis can result in significant morbidity, vascular complications, and death since specific therapy depends on underlying aetiology and pathology. This case series highlights three patients presenting with mycotic pseudoaneurysm, infectious occlusive iliac thrombus relative to a chronic state of immunosuppression, infections, and malignancy associated with Crohn-related fistulas, Campylobacter fetus bacteraemia, and paraneoplastic aetiologies, resulting in poor patient outcomes. It is crucial to distinguish primary vasculitis from secondary aetiologies and mimickers, as misdiagnosis can lead to unnecessary, potentially harmful treatments and delay in surgical interventions if indicated.

Platelet activation is constrained by endothelial-derived prostacyclin (PGI2) through cyclic adenosine-3',5'-monophosphate (cAMP) signaling involving multiple isoforms of adenylyl cyclase (AC). The roles of specific AC isoforms in controlling hemostasis remain unclear and require clarification. To understand the specific contribution of AC6 in platelet hemostatic and thrombotic function. A platelet-specific AC6 knockout mouse was generated. Biochemical approaches were used to determine intracellular signaling, with flow cytometry, tail bleeding time assays, and in vivo thrombosis by ferric chloride were used to measure the hemostatic and thrombotic importance of platelet AC6. Loss of AC6 resulted in diminished accumulation of platelet cAMP in response to PGI2, while basal cAMP was unaffected. We found no differences in phosphodiesterase 3A activity, suggesting the defect was in generation rather than hydrolysis of cAMP. Consistent with this, phosphorylation of protein kinase A substrates, vasodilator-stimulated phosphoprotein, and glycogen synthase kinase were diminished but not ablated. Functional studies demonstrated that the inhibition of thrombin-induced fibrinogen binding and P-selectin expression by PGI2 was severely compromised, while inhibition of glycoprotein VI-mediated platelet activation was largely unaffected. Under conditions of flow formed stable thrombi, but in the absence of AC6, thrombi were insensitive to PGI2. Diminished in vivo sensitivity to PGI2 manifested as significantly reduced tail bleeding and accelerated occlusive arterial thrombus formation in response to vascular injury that were highly unstable and prone to embolization in AC6 knockout mice. These data demonstrate that AC6 is linked directly to PGI2-mediated platelet inhibition and regulation of hemostasis and thrombosis in vivo.